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Biomedical subjects

J Benoit

Publications and source records attributed to J Benoit.

At least 19 recordsLinked to original sources

Oxaliplatin loaded PLAGA microspheres: design of specific release profiles.

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.

Antineoplastic Agents↗

The effect of gamma-irradiation on drug release from bioerodible microparticles: a quantitative treatment.

The two major objectives of this study were: (i) to monitor the effect of different gamma-irradiation doses (4-33 kGy) on the release kinetics from 5-fluorouracil (5-FU)-loaded poly(D,L-lactide-co-glycolide) (PLGA)-based microparticles, and (ii) to analyze the obtained experimental data with a new mathematical model giving insight into the occurring mass transport phenomena. Drug release was found to depend significantly on the applied gamma-irradiation dose. Interestingly, the obtained release profiles were all biphasic: a rapid initial drug release phase ("burst") was followed by a slower, approximately constant drug release phase. Surprisingly, only the initial rapid drug release was accelerated by gamma-irradiation; the subsequent zero-order phase was almost unaffected. Importantly, the new mathematical model which is based on Fick's second law of diffusion and which considers polymer degradation was applicable to all the investigated systems. In addition, the gamma-irradiation dose could be quantitatively related to the resulting drug release rate. In conclusion, diffusion seems to be the dominating release rate controlling mechanism in all cases, with a significant contribution of the polymer degradation process.

Antimetabolites, Antineoplastic↗

[Total hip arthroplasty and femoral head osteonecrosis in renal transplant recipients].

PURPOSE OF THE STUDY: Osteonecrosis of the femoral head is reported in a very variable proportion of renal transplant recipients. When these patients require total hip arthroplasty (THA), immunosuppression and poor bone quality increase the risk of aseptic loosening and infection. In the literature, functional outcome has been satisfactory although rates of early and late complications have varied greatly. The purpose of our work was to determine the long-term outcome in a series of renal graft recipients who underwent THA for osteonecrosis of the femoral head. MATERIAL AND METHODS: Forty-eight THA were implanted for aseptic osteonecrosis of the femoral head (Ficat grade III and IV) in 32 renal transplant recipients between 1974 and 1995 (21 men and 11 women). Mean age was 30 years at transplantation and 39 years at THA surgery. Thirty patients had been on hemodialysis for a mean 1 year prior to transplantation. Joint disease concerned 2 or more joints in 23 of the 32 patients. Fifteen hips had a surgical history: 8 drillings and 3 head arthroplasties. The THA was implanted under general anesthesia via the posterolateral approach. All implants were fixed with a gentamycin cement. A cephalosporin was used for the antibiotic prophylaxis in 20 cases and a cephalosporin/vancomycin combination in 24. Functional outcome was assessed with the Postel-Merle-d'Aubigné (PMA) score. Functional gain was [(PMAreview-PMApreop)/PMApreop]. General or local complications were recorded at last follow-up. The complete or incomplete nature of lucent lines seen on the last follow-up x-rays and their evolution were also recorded. Reasons for second procedures were noted. RESULTS: Early complications were: phlebitis (n=1), hematoma (n=7), dislocation (n=1), deep infection (n=2). At last follow-up (mean=5 years 7 months), four patients (6 THA) had died and six (7 THA) were lost to follow-up. Preoperatively, function was scored fair or poor in 91% of the patients. At last follow-up function was scored good, very good, or excellent in 75%. Mean functional gain was 38%. A second operation was necessary for seven THA due to aseptic loosening (mean delay 9 years 10 months), for five others for septic loosening (mean delay 6 years 8 months), and finally for two for instability (one early and the other after more than 2 years). In all, 29% of the THA were reoperated. Two deaths were related to late THA infection. Active lucent lines were observed in 11% of the THA (excepting patients reperated for loosening). DISCUSSION: The functional gain provided by THA in renal transplant recipients with aseptic osteonecrosis of the femoral head is clearly established. Implant survival remains a problem. The rate of early local complications was high in our series, mainly related to hematoma formation and infection. The infections observed were particularly severe requiring early comprehensive management at onset of clinical signs. For patients with suspected deep infection, we propose an aspiration biopsy of the joint to obtain a bacteriological sample. CONCLUSION: THA enables good functional outcome for renal transplant recipients suffering from osteonecrosis of the femoral head, but at the cost of a high risk of early and long-term complications not always reported in the literature.

Activities of Daily Living↗

Impact of a modified apical dissection during radical retropubic prostatectomy on the occurrence of positive surgical margins: a comparative study in 212 patients.

OBJECTIVES: To assess the impact of a modified technique of apical dissection during radical retropubic prostatectomy on the occurrence of positive surgical margins (PSMs). METHODS: Between 1992 and 1998, 212 nonconsecutive patients with localized prostate cancer (57 T1, 155 T2) underwent radical retropubic prostatectomy and were divided into two groups: group 1, 85 patients who underwent surgery before January 1994; and group 2, 127 patients who underwent surgery with the modification of the apical dissection after January 1994. The modified technique consisted of a wide excision of periprostatic soft tissue at the apex, including the bilateral neurovascular bundles. The clinical data (age, prostate-specific antigen, clinical staging) and pathologic findings (pathologic staging, Gleason score, PSM rate) of the two groups were compared. RESULTS: No significant difference was found between the two groups regarding the median prostate-specific antigen level (10.8 ng/mL and 9.5 ng/mL), Gleason score, and pathologic staging. Overall, the PSM rate was 53% in group 1 and 20.5% in group 2 (P <0.001). The number of PSMs decreased 2.6-fold in group 2. The PSM rate was significantly reduced at the apex with the new technique (group 1, 33.3%; group 2, 7.7%; P = 0.008). The PSM rate expressed with the odds ratio was 4.4-fold lower for patients in group 2 than for those in group 1. CONCLUSIONS: The modified apical dissection in radical retropubic prostatectomy significantly improves the PSM rate in patients with localized T1-T2 prostate cancer.

Aged↗

Cerebral autoregulation in orthostatic intolerance.

Many of the primary symptoms of orthostatic intolerance (fatigue, diminished concentration) as well as some of the premonitory symptoms of neurally mediated syncope (NMS) are thought to be due to cerebral hypoperfusion. Transcranial Doppler measurements of middle cerebral artery blood velocity (CBV) is at present the only technique for assessing rapid changes in cerebral blood flow, and hence for evaluating dynamic cerebral autoregulation. However, controversies exist regarding data interpretation. At syncope, during the collapse of blood pressure (BP), diastolic CBV diminishes, whereas systolic CBV is maintained. Some consider this increase in CBV pulsatility to be indicative of a paradoxical increase in cerebrovascular resistance (CVR) prior to syncope. Others note that mean CBV decreases much less than does mean BP, implying that cerebral autoregulatory mechanisms are intact and functioning at syncope. Similarly, there is no evidence of impaired dynamic cerebral autoregulation, as measured by standard linear transfer-function analysis, in patients with NMS. Some patients with exaggerated postural tachycardia (POTS) have been found to have an excessive decrease in CBV during head-up tilt. Controversy exists as to whether this decrease results from an excessive sympathetic outflow to the cerebral vasculature or from hyperventilation. However, many other equally symptomatic patients with a similar hemodynamic profile of exaggerated tachycardia during head-up tilt have normal CBV changes during this maneuver and have normal dynamic cerebral autoregulation as determined by transfer-function analysis. Whether these discrepancies reflect different pathologies in patients with POTS is currently unknown.

Animals↗

Dynamic cerebral autoregulation is preserved in neurally mediated syncope.

To test whether cerebral autoregulation is impaired in patients with neurally mediated syncope (NMS), we evaluated 15 normal subjects and 37 patients with recurrent NMS. Blood pressure (BP), heart rate, and cerebral blood velocity (CBV) (transcranial Doppler) were recorded at rest and during 80 degrees head-up tilt (HUT). Static cerebral autoregulation as assessed from the change in cerebrovascular resistance during HUT was the same in NMS and controls. Properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between BP and CBV estimated from filtered data segments (0.02-0.8 Hz). During the 3 min preceding syncope, dynamic cerebral autoregulation of subjects with NMS did not differ from that of controls nor did it change over the course of HUT in patients with NMS or in control subjects. Dynamic cerebral autoregulation was also unaffected by the degree of orthostatic intolerance as inferred from latency to onset of syncope. We conclude that cerebral autoregulation in patients with recurrent syncope does not differ from that of normal control subjects.

Adult↗

Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide.

Huntington's disease (HD) results from the degeneration of striatal neurones, mainly gamma-aminobutyric acid (GABA)ergic projection neurones and lately cholinergic interneurones. The use of trophic factors as agents able to prevent such neural degeneration is a promising strategy. The aim of this study was to validate nerve growth factor-loaded (NGF-loaded) poly-D,L-lactide-co-glycolide (PLGA) microspheres for treatment of HD in a rat model with quinolinic acid lesion using autoradiographic study of D2 dopaminergic receptors (D2R). This target is expressed by about half of striatal neurones and its scintigraphic exploration has already been performed for the follow-up of this degenerative process. Ex vivo autoradiography of D2R performed with iodobenzamide, the widely used ligand for single photo emission computerized tomography, revealed slight neuroprotection. Moreover, tolerance of microspheres was demonstrated by in vitro autoradiography with the marker of gliosis, [(3)H]-PK 11195.

Animals↗

Arthroscopic treatment of bilateral humeral head osteonecrosis.

A 37-year-old woman with a renal transplant was treated by arthroscopic debridement for bilateral steroid-induced humeral head osteonecrosis. Radiologically, the right shoulder had been categorized as stage III and the left as stage IV according to Arlet and Ficat. Relief of pain and improved range of motion were obtained especially on the right shoulder. Arthroscopy is an efficient procedure for treatment of humeral head osteonecrosis in the renal transplant recipient including radiological stages III with episodes of locking.

Adrenal Cortex Hormones↗

Orthostatic intolerance in the chronic fatigue syndrome.

This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS). Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical suspicion as to the likelihood of observing laboratory evidence of OI was assigned. Laboratory investigation consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing (6 breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched healthy controls who had no history of OI were used to define the range of normal responses to these three maneuvers. Forty percent of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva maneuver and to deep breathing were similar in controls and patients. On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in patients with OI than in those without OI. We conclude that there exists a clinically identifiable subgroup of patients with CFS and OI that differs from control subjects and from those with CFS without OI for whom treatment specifically aimed at improving orthostatic tolerance may be indicated.

Adult↗

Wrist arthroscopy and dislocation of the radiocarpal joint without fracture.

The authors report a rare case of dorsal dislocation of the radiocarpal joint without any bony lesion associated. The traumatic cause was a high energy motorbike accident. Fractures of the other limbs were associated. The authors report the clinical, radiological, and arthroscopic features. Wrist arthroscopy showed a complete tear of all the extrinsic ligaments, a radial avulsion of the triangular fibrocartilage complex, and the integrity of the intracarpal ligaments, which guided the treatment. The dislocation was treated by closed reduction and radiocarpal pinning. The authors propose wrist arthroscopy in radiocarpal dislocation for diagnosis of soft tissue and cartilaginous lesions to guide the treatment (close or open).

Accidents, Traffic↗

Persistent functional and structural retinal anomalies in newborn rats exposed to hyperoxia.

Previous studies have shown that newborn rats exposed postnatally to hyperoxia will develop a permanent impairment of the retinal function as determined with the electroretinogram (ERG). The purpose of our study was to examine whether postnatal hyperoxia equally alters the light- and dark-adapted ERGs and oscillatory potentials (OPs) as well as leads to permanent structural modification of the retina. During the first 14 days of life, cohorts of Sprague-Dawley rats were exposed to a hyperoxic environment, and ERGs were recorded at mean ages of approximately 25 and 55 days. Our results indicate that both light- and dark-adapted ERGs and OPs are already significantly altered within a few days following exposure to hyperoxia. None of the ERG and (or) OP parameters, with the exception of the a-wave, returned to normal values by 55 days of age. In fact some dark-adapted OPs were completely abolished following postnatal O2 exposure. Histological analysis revealed that the retina of rats exposed to hyperoxia failed to develop an outer plexiform layer and had a reduced count of horizontal cells, consistent with the permanent postreceptoral anomalies seen in the ERG responses. Our results suggest that postnatal hyperoxia causes a generalized retinal disorder leading to permanent structural modifications of the retinal cytoarchitecture and lasting anomalies of the rod and cone functions.

Age Factors↗

Aseptic avascular necrosis of the femoral condyles in renal transplant patients: clinical and radiological aspects on 69 knees.

The purpose of this study was to analyze clinical and radiological aspects of aseptic avascular necrosis (AVN) of the femoral condyles in renal transplant patients. Forty-five renal transplant patients were followed between 1971 and 1993, and 69 knees have been studied. The immunosuppressive protocol comprised in all cases corticosteroids, with aziathioprine and since 1983 cyclosporin in 80% of patients. Episodes of rejection were treated with bolus doses of methylprednisolone. In 53.3% of patients, both knees were involved. The necrosis was bicondylar in 60.8% of knees. In the case of an unicondylar lesion, the lateral condyle was involved in 24.7% of knees vs 14.5% for the medial condyle. Symptoms occurred on average 4.9 years after transplantation (range 3 months-10.5 years). This period appeared significantly shorter for patients who had suffered an episode of rejection. In only 24.4% of patients was the knee involvement isolated. Pain was the initial symptom for 83% of patients. Other symptoms included locked knee (20.7%), effusion (49.2%), instability (14.5%), and loss of motion (15.9%). The diagnosis was established by standard radiographs, and in 8 patients by magnetic resonance imaging. Aseptic AVN of the femoral condyles in renal transplant patients is not rare even if it is less frequent than femoral head necrosis. Medication with corticosteroids is the main risk factor.

Adolescent↗

New healing agent for colonic anastomosis.

This study evaluated the healing property, on colonic anastomoses, of a new compound termed RGTA11 (standing for "regenerating agent," a dextran derivative with heparin-like properties). Colonic anastomoses were performed in 183 adult rats after dipping both ends of the colon in solutions containing RGTA11. The anastomoses were made end-to-end on a single plan, 8 sutures. Healing was evaluated mechanically by the bursting pressure in 108 animals and histological analysis in 75. Results indicated that after 48 h RGTA11-treated animals presented a twofold increased resistance to anastomoses breakage (P < 0.01) over nontreated (saline buffer) animals. After 96 h and until day 7 there was no longer a difference between study and control animals. Although this difference in breakage was not readily observed at histological level, results suggest that RGTA11 could be used to aid colonic anastomosis healing. RGTA11 is of potential clinical interest in this regard since complications that are known to occur postoperatively result from early leakage.

Anastomosis, Surgical↗

Glomus tumor of the fat pad.

The authors report an exceptional glomus tumor location in Hoffa's ligament in a 65-year-old man. Based on this observation and a literature review, the authors provide the clinical and radiographic diagnostic appearances of this type of tumor. Surgical removal of the tumor achieved immediate disappearance of knee pain. Histological examination of the tumor has established the definitive diagnosis.

Adipose Tissue↗

Evidence supportive of a functional discrimination between photopic oscillatory potentials as revealed with cone and rod mediated retinopathies.

We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs.

Adolescent↗

Hemiretinal contribution to the timing of the full-field PVEP as determined with the motor reaction time.

With the use of the simple motor reaction time (RT), we examined the contribution of the hemiretinas to the timing of the pattern reversal visual evoked potential (PVEP). RTs were obtained to the reversal of a progressively dimmer check falling either on the central, nasal, temporal, superior or inferior retina. Results were correlated with the peak time of the P1 wave evoked to the reversal of the entire checkerboard stimulus to the same luminance conditions as that used to generate the RT measurements. Our results clearly indicate that the time taken to trigger a manual response depends not only on the luminance of the stimulus, but also on where it falls on the retina. Comparing the above data with the peak time of the PVEP obtained to the reversal of the entire screen indicates that at brighter luminance the peak time of the P1 wave correlates with that measured from the most central retina, while at dimmer intensities it correlates with the mathematical average of all the retinal locations tested.

Adult↗

Cerebrovascular and cardiovascular measurements during neurally mediated syncope induced by head-up tilt.

BACKGROUND AND PURPOSE: This study examines changes in systemic hemodynamics and in cerebral blood velocity that occur during neurally mediated syncope (NMS) to determine whether cerebral autoregulation is intact or impaired in patients with recurrent NMS. METHODS: Beat-to-beat recordings of heart rate, blood pressure (volume clamp photoplethysmography), stroke volume (impedance cardiography), and right middle cerebral artery blood velocity (transcranial Doppler sonography) were performed at rest and during 80 degrees head-up tilt. Twelve patients with NMS and 10 healthy control subjects were studied. RESULTS: Baseline values and the initial response to head-up tilt of control subjects and patients with NMS were similar. The mean latency to onset of syncope was 11.8 +/- 11.1 minutes. At syncope, heart rate, systolic and diastolic blood pressure, and diastolic cerebral blood velocity decreased significantly, whereas systolic cerebral blood velocity did not change. Calculated cerebrovascular resistance was significantly reduced from 1.85 +/- 0.60 to 1.32 +/- 0.27 mm Hg/cm per second, whereas the pulsatility index increased from 0.92 +/- 0.16 to 1.52 +/- 0.21. We never observed a change in cerebral blood velocity before the rapid decline in blood pressure, nor did we observe any significant change in respiratory pattern. CONCLUSIONS: The decrease in cerebrovascular resistance during NMS indicates that the integrity of cerebrovascular autoregulation is maintained even when syncope is imminent. The selective loss of diastolic flow during syncope and the increase in pulsatility index are likely caused by collapse of downstream vessels as diastolic blood pressure decreases below the critical closing pressure of cerebral vessels.

Adult↗